Arylaminoalcohol compound



Patented June 24, 1930 UNITED STATES:

PATENT OFFICE ROGER ADAMS, OF URBANA, ILLINOIS, ASSIGNOR TO ABBOTTLABORATORIES, OF NORTH CHICAGO, ILLINOIS, A CORPORATION OF ILLINOISABYLAMINOALOOHOL COMPOUND No Drawing.

My invention relates to the preparation of compounds of the generalformula as an alkyl, and R" O-CHOH ommNR'R',

where R represents an alkylgroup, R represents an aliphatic hydrocarbonradical such represents hydrogen or an aliphatic hydrocarbon radicalcontaining more than one carbon atom.

These compounds are of therapeutic value. They cause a rise in bloodpressure and exert a so-called sympathomimetic eflect.

These amines may be produced by several series of reactions, and thefollowing equations will illustrate one ofthe ossible metholds which maybe employed or their synt esis:

1. Oooommx+mmw reduction 2. O-coomnmmv O-onon CH(R)NR'R' where Xrepresents a halogen, and R, R, and R represent the atoms or radicalsalready indicated. These reactions may be carried on as follows Asolution containing 2.5 molecular equivalents of the desired amine,HNRR", is placed in a flask equipped with a thermometer, stirrer, andmeans for temperature control. The amine solution is preferably of about30% strength, and the solvent may be water or an organic liquid, such asalcohol. To this solution, cooled to about '5 C., is

slowly added one molecular equivalent of the compound Application filedJanuary 27, 1928. Serial No. 250,076.

after the ether extraction is neutralized with cold dilute sodiumhydroxide solution, the

base

C H COCH (R) NRR" extracted with an immiscible solvent like other orbenzene, the extract dried, and the solvent removed. Ice is then added,and the base is neutralized with hydrochloric acid,

and the solution evaporated practically to dryness. The residue is takenup in alcohol, decolorizedby carbon black, acetone added, andthecrystalline material removed by filtration. It may be further purifiedby redissolving in alcohol or chloroform, followed by the addition'ofacetone. The ketone hydrochlorides,

O H OOCH (R )NRR".HCI, so obtained are white crystalline solids, readilysoluble in water.

The above ketones may be reduced by several methods; my preferred methodis to reduce catalytically by, means of platinum oxide, according tothe'method of Adams and Shriner (Journal of the American ChemicalSociety, 45, 2171 (1923). For example, the required amount of platinumoxide is placed in a stout glass bottle, covered with alcohol.

and reduced by hydrogen. By means of 0.5 gram of catalyst so prepared,30 grams of the above ketone hydrochloride, dissolved in the leastfeasible quantity of absolute alcohol, is reduced in the bottle byhydrogen at a 30 to 40 pounds pressure. The reduction is ordinarilypractically complete in one-half hour. The platinum oxides are removedby filtration, the alcohol solution. concentrated, and the reduced aminocompound, having the general formula CJLCHOH CH(R)NRR".HC1 is allowed tocrystallize. It! is recrystallized from alcohol. The compounds soobtained are white crystalline solids, havi n rather high meltingpoints, and being readily soluble in water, less so in organic solvents.

.By this general method there have been 'prepared the followingcompounds. In the table, the symbols R, R, and R" slgmfy groups asalready defined. All temperatures are given in degrees Centigrade.

I H Melting point of intermediate Meltin int 0! R R R oimooomnmn'amnciomlononozi mn'nmnol Methyl Ethyl Hydrogen 183-184 190191 Methyl EthylEthyl 167-168 %6:-

Methyl n-Propyl Hydrogen 180 218 Methyl Iso-Propyl Hydrogen 213-213. 5103 0 Methyl n-Butyl Hydrogen 158-159 2%2-221 Methyl n-Amyl Hydrogen 150219 n Ethyl Methyl Hydrogen 190-192 IM -190 n-Propyl Methyl Hydrogen182-184 224 4 The scope of the invention should be determined byreference to the appended claims,- said claims being construed asbroadly as pos-. sible consistent with the state of the art.

I claim as my invention:

1. As a new article of manufacture, a compound of the general formulawhere R represents an alkyl group, R represents a monovalent saturatedaliphatic hydrocarbon radical, and R represents a hydrogen or amonovalent saturated aliphatic hydrocarbon radical ontaining more thanone carbon atom, and the R, R, and R" substituents together contain notless than 3 carbon atoms.

2. As a new article of manufacture, a compound of the general formulaO-onononmmma,

where R represents an alkyl group, and R represents a monovalentsaturated aliphatic hydrocarbon radical, where the R and R substituentstogether contain not less than 3 carbon atoms.

Jan. 24, 1928. 1

ROGER ADAMS.

